Re-expression of N-cadherin in remyelinating lesions of experimental inflammatory demyelination

Abstract

The cell adhesion molecule N-cadherin is involved in several processes during central nervous system development, but also in certain pathologic conditions in the adult brain, including tumorigenesis and Alzheimer's disease. N-cadherin function in inflammatory demyelinating disease has so far not been investigated. In vitro studies suggest a role of N-cadherin in myelination; on the other hand N-cadherin has been implicated in the formation of the glial scar, which is believed to impede remyelination. The aim of our study was to investigate the expression pattern of N-cadherin immunoreactivity in experimental autoimmune encephalomyelitis induced by myelin oligodendrocyte glycoprotein (MOG-EAE), an animal model closely mimicking multiple sclerosis. It allows a detailed evaluation of all stages of de- and remyelination during lesion development. Immunopathological evaluation was performed on paraffin-embedded CNS sections sampled at days 20 to 120 post immunization. We found a predominant expression of N-cadherin on oligodendrocytes in early remyelinating lesions, while in fully remyelinated shadow plaques there was no detectable immunoreactivity for N-cadherin. This expression pattern indicates a role of N-cadherin in the initiation of remyelination, most likely by providing a guidance between myelin lamellae and oligodendrocytes. Once the initial contact is made N-cadherin is then rapidly downregulated and virtually absent after completion of the repair process, analog to its known role in developmental myelination. Our results show that N-cadherin plays an important role in creating a remyelination-facilitating environment.